The causes of alcoholic cardiomyopathy were investigated by studying cardiac protein synthesis in the isolated heart perfused with ethanol or acetaldehyde. Although ethanol did not inhibit protein synthesis until lethal levels, the synthesis was decreased by 50% by acetaldehyde at levels found in intoxicated humans (0.1-0.2 mM). Similarly, cardiac microsomal protein synthesis in vitro was decreased at levels of 0.03 mM acetaldehyde. The specific proteins affected e.g., myosin, are now being studied. The cardiac protein response to hypertension in vitro was studied by measuring protein degradation during the interval of stress when increased protein synthesis is regularly seen. The measurement of degradation were complicated by the reutilization for new synthesis of amino acids released by protein breakdown. Reutilization was stopped by blocking new protein synthesis with puromycin. With both a reutilized (C14-lysine) and a minimally reutilized (C14-phenylalamine) amino acid as tracers, degradation of cardiac mixed protein did not increase during the early period of hypertension in vitro when increased protein synthesis first appears. The difference in cardiac response to hypertension or volume loading was studied with a new in vitro cardiac perfusion system where varied loads may be presented to the right ventricle while coronary flow is rigidly controlled by a separate perfusion system. As pulmonary tension is increased, increased right ventricular work is initially accompanied by augmented protein synthesis whereas increased volume loading with the same coronary flow does not show the same increase in 3 hours of stress.